Processes and reagents for making diaryliodonium salts

Patent metadata

Field	Value
Publication number	US-9278959-B2
Application number	US-201313905668-A
Country	US
Kind code	B2
Filing date	May 30, 2013
Priority date	Jun 5, 2012
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

This invention relates to processes and reagents for making diaryliodonium salts, which are useful for the preparation of fluorinated and radiofluorinated aromatic compounds.

First claim

What is claimed is:

1. A process for making a compound of Formula I:

comprising:
treating a compound of Formula II:
Ar 1 —I  II

with (A) a tetravalent silicon moiety having at least one X group bound to Si, wherein each X is, independently, a ligand that is a conjugate base of an acid HX, wherein HX has a pKa of less than or equal to 12; and is selected from the group consisting of halide, aryl carboxylate, alkyl carboxylate, phosphate, phosphonate, phosphonite, azide, thiocyanate, cyanate, phenoxide, triflate, thiolates, and stabilized enolates; and
(B) (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), (1-fluoro -4-methyl-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), or an optionally substituted N -fluoropyridinium tetrafluoroborate;
wherein:
Ar 1 is selected from the group consisting of:

wherein Ar is an optionally substituted aryl or heteroaryl, wherein Ar does not have unprotected protic groups; and P 1 , P 2 , P 3 , P 4 , P 5 , and P 6 are each, independently, protecting groups.

2. The process of claim 1 , wherein the process is carried out in the absence of added acid.

3. The process of claim 1 , wherein the process utilizes (1-chloromethyl-4-fluoro -1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate).

4. The process of claim 1 , wherein the process utilizes (1-fluoro-4-methyl-1,4-diazoniabicyclo [2.2.2]octane) bis(tetrafluoroborate).

5. The process of claim 1 , wherein the process utilizes N-fluoro-2,3,4,5,6-pentachloropyridinium tetrafluoroborate.

6. The process of claim 1 , wherein the process utilizes less than 2 equivalents of (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), (1-fluoro-4-methyl-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), or optionally substituted N -fluoropyridinium tetrafluoroborate for 1 equivalent of the compound of Formula II.

7. The process of claim 1 , wherein the process utilizes less than 1.5 equivalents of (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), (1-fluoro-4-methyl-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate), or optionally substituted N -fluoropyridinium tetrafluoroborate for 1 equivalent of the compound of Formula II.

8. The process of claim 1 , wherein each X is, independently, a ligand that is a conjugate base of an acid HX, wherein HX has a pKa of less than or equal to 5.

9. The process of claim 1 , wherein each X is O(C═O)CH 3 .

10. The process of claim 1 , wherein the tetravalent silicon moiety is (R 1 ) 3 Si—X, wherein each R 1 is, independently, C 1-12 alkyl or aryl.

11. The process of claim 10 , wherein each R l is methyl.

12. The process of claim 10 , wherein (R 1 ) 3 Si—X is (CH 3 ) 3 Si—X.

13. The process of claim 10 , wherein (R 1 ) 3 Si—X is (CH 3 ) 3 Si—O(C═O)CH 3 .

14. The process of claim 1 , wherein the process utilizes 2 equivalents or more of the tetravalent silicon moiety for 1 equivalent of the compound of Formula II.

15. The process of claim 1 , wherein the process utilizes 2.5 equivalents to 3 equivalents of the tetravalent silicon moiety for 1 equivalent of the compound of Formula II.

16. The process of claim 15 , wherein the tetravalent silicon moiety is (R 1 ) 3 Si—X, wherein each R 1 is, independently, C 1-12 alkyl or aryl.

17. The process of claim 1 , wherein the processes comprises treating a compound of Formula II with (CH 3 ) 3 Si—O(C═)CH 3 ; and (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate).

18. The process of claim 1 , wherein the processes comprises treating a compound of Formula II with 2.5 equivalents to 3 equivalents of (CH 3 ) 3 Si—O(C═ 0 )CH 3 ; and less than 1.5 equivalents of (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane) bis(tetrafluoroborate).

19. A process for making a compound of Formula III:

wherein Ar 2 is an optionally substituted aryl or heteroaryl, the process comprising:
treating a compound of Formula II:
Ar 1 —I  II

with (A) a tetravalent silicon moiety having at least one X group bound to Si, wherein each X is, independently, a ligand that is a conjugate base of an acid HX, wherein HX has a pKa of less than or equal to 12; and is selected from the group consisting of halide, aryl carboxylate, alkyl carboxylate, phosphate, phosphonate, phosphonite, azide, thiocyanate, cyanate, phenoxide, triflate, thiolates, and stabilized enolates; and
(B) (1-chloromethyl-4-fluoro-1 ,4-diazoniabicyclo [2.2.2]octane) bis(tetrafluoroborate), (1-fluoro-4-methyl-1,4-diazoniabicyclo [2.2.2]octane) bis(tetrafluoroborate), or an optionally substituted N-fluoropyridinium tetrafluoroborate;
wherein:
Ar 1 is selected from the group consisting of:

Assignees

• Nutech Ventures

Inventors

• Dimagno Stephen

Classifications

• C07C71/00

  Esters of oxyacids of halogens · CPC title

• C07C255/55

  containing cyano groups and esterified hydroxy groups bound to the carbon skeleton · CPC title

• C07D277/30

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07C271/22

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07C253/30

  by reactions not involving the formation of cyano groups · CPC title